{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:15:24Z","timestamp":1789478124100,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG059627"],"award-info":[{"award-number":["R01 AG059627"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG062500"],"award-info":[{"award-number":["R01 AG062500"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There is an urgent need to identify modifiable environmental risk factors that reduce the incidence of Alzheimer's disease (AD). The B\u2010like vitamin choline plays key roles in body\u2010 and brain\u2010related functions. Choline produced endogenously by the phosphatidylethanolamine N\u2010methyltransferase protein in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. ~90% of Americans do not reach the recommended daily intake of dietary choline. Thus, it's imperative to determine whether dietary choline deficiency increases disease outcomes. Here, we placed 3xTg\u2010AD, a model of AD, and non\u2010transgenic (NonTg) control mice on either a standard laboratory diet with sufficient choline (ChN; 2.0\u00a0g\/kg choline bitartrate) or a choline\u2010deficient diet (Ch\u2010; 0.0\u00a0g\/kg choline bitartrate) from 3 to 12 (early to late adulthood) months of age. A Ch\u2010 diet reduced blood plasma choline levels, increased weight, and impaired both motor function and glucose metabolism in NonTg mice, with 3xTg\u2010AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, elevated soluble and insoluble Amyloid\u2010\u03b2 and Thioflavin S structures, and tau hyperphosphorylation at various pathological epitopes in the hippocampus and cortex of 3xTg\u2010AD Ch\u2010 mice. To gain mechanistic insight, we performed unbiased proteomics of hippocampal and blood plasma samples. Dietary choline deficiency altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, dietary choline deficiency altered protein networks associated with insulin metabolism, mitochondrial function, inflammation, and fructose metabolic processing. Our data highlight that dietary choline intake is necessary to prevent systems\u2010wide organ pathology and reduce hallmark AD pathologies.<\/jats:p>","DOI":"10.1111\/acel.13775","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:56Z","timestamp":1673827256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Dietary choline intake is necessary to prevent systems\u2010wide organ pathology and reduce Alzheimer's disease hallmarks"],"prefix":"10.1111","volume":"22","author":[{"given":"Nikhil","family":"Dave","sequence":"first","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Judd","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"},{"name":"Arizona Alzheimer's Consortium  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Decker","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Winslow","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Sarette","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Villarreal\u00a0Espinosa","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Tallino","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"},{"name":"Arizona Alzheimer's Consortium  Phoenix Arizona USA"},{"name":"School of Life Sciences Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha K.","family":"Bartholomew","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"},{"name":"Arizona Alzheimer's Consortium  Phoenix Arizona USA"},{"name":"School of Life Sciences Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Bilal","sequence":"additional","affiliation":[{"name":"Translational Cardiovascular Research Center and Department of Internal Medicine University of Arizona College of Medicine  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Sandler","sequence":"additional","affiliation":[{"name":"Biosciences Mass Spectrometry Facility, Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"McDonough","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna K.","family":"Winstone","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"},{"name":"Arizona Alzheimer's Consortium  Phoenix Arizona USA"},{"name":"School of Life Sciences Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A.","family":"Blackwood","sequence":"additional","affiliation":[{"name":"Translational Cardiovascular Research Center and Department of Internal Medicine University of Arizona College of Medicine  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Glembotski","sequence":"additional","affiliation":[{"name":"Translational Cardiovascular Research Center and Department of Internal Medicine University of Arizona College of Medicine  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Karr","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"},{"name":"Biosciences Mass Spectrometry Facility, Biodesign Institute Arizona State University  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7722-0533","authenticated-orcid":false,"given":"Ramon","family":"Velazquez","sequence":"additional","affiliation":[{"name":"Arizona State University\u2010Banner Neurodegenerative Disease Research Center at the Biodesign Institute Arizona State University  Tempe Arizona USA"},{"name":"Arizona Alzheimer's Consortium  Phoenix Arizona USA"},{"name":"School of Life Sciences Arizona State University  Tempe Arizona 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(1998).A Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate Other B Vitamins and Choline and Subcommittee on Upper Reference Levels of Nutrients. Retrieved June 23 2022 from Dietary Reference Intakes for Thiamin Riboflavin Niacin Vitamin B6 Folate Vitamin B12 Pantothenic Acid Biotin and Choline website:http:\/\/www.nap.edu\/catalog\/6015.html"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11248\u2010019\u201000166\u2010x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.08.018"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(20)30071\u20105"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X11430859"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/c6cs00731g"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0115922"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8073516"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.770863"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010017\u20102737\u20100"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00086"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394\u2010016\u20101296\u20108"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12084"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00359"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/DNEU.22327"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PHRS.2018.03.010"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EXGER.2020.110882"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1242\/DMM.036806"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2022.100207"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKY1131"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PBB.2017.05.011"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13037"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12775"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010018\u20100322\u2010z"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.06.003"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2021.796867\/BIBTEX"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmz115"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3905719"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/AJCN\/NQAC193"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9050445"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13775","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13775","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13775","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T21:27:45Z","timestamp":1692566865000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,15]]},"references-count":45,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1111\/acel.13775"],"URL":"https:\/\/doi.org\/10.1111\/acel.13775","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.08.14.503929","asserted-by":"object"}]},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,15]]},"assertion":[{"value":"2022-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13775"}}